Project Summary An elusive problem plagues the treatment of glaucoma: our inability to measure intraocular pressure (IOP) continuously in patients with the disease. Instead, we still rely on measurements taken at irregular intervals in ophthalmologists' or optometrists' offices, or worse on unwieldy home devices which extrapolate IOP measurements from external factors and, as such, likely do not give a true measurement of IOP. Not only is continuous measurement still unexplored territory, but so is the understanding of temporal variability of both IOP and intracranial pressure (ICP) and their link in the pathogenesis of glaucoma. A continuous, micromachined pressure sensor which is chronically implantable in both the eye and the brain and capable of measuring and reporting these pressures in real time is truly the holy grail of glaucoma science and treatment. While devices have been developed to try to solve this problem, thus far they have been plagued by problems of drift and biofouling. This K08 Career Development Award for Damien Rodger, MD, PhD, based at the world- class USC Roski Eye Institute, will put in motion all that is needed for him to further pursue the development of a novel pressure sensor enabled by a breakthrough encapsulation technology to study this likely causative link between ICP and IOP, while at the same time enabling him to engage with the mentors and collaborators needed to foster his career. It will give him the ability to round out his skillset in areas where he has identified gaps ? research methodology and study design, biostatistics, ocular pathology and neuropathology as they relate to biomedical implants and glaucomatous optic nerve damage, and technology transfer. The research will focus on 1) in vitro and ex vivo studies of the breakthrough pressure sensor technology, 2) in vivo testing of the accuracy, stability, and biocompatibility of the continuous IOP sensor when implanted chronically in an animal model of ocular hypertension and the correlations of mean IOP and IOP variability with glaucomatous optic nerve damage, and 3) simultaneous in vivo measurement of ICP and IOP continuously in an animal model of intracranial hypotension with subsequent assessment of optic nerve damage and sensor biocompatibility. The results from this research will not only enlighten the community as to the critical ICP and IOP link, also known as the translaminar gradient, which has been for a long time sitting on at the cusp of being fully embraced, but also bring to fruition the necessary technology, skills, and data for Dr. Rodger to garner R01 funding on a pipeline to career independence. Combined, these results and additional training will enable the devices to quickly find their ultimate use in alleviating human suffering.